Endocrine abnormalities occur either as ?self-defined? disorders or in combination with other diseases. An ever-increasing number of ?non-endocrine? diseases also are found to be associated with endocrine abnormalities. Optimal use of valid laboratory tests and correct diagnosis of endocrine diseases or the endocrine components of ?non-endocrine? diseases obviously are important both medically and economically. Recently, we studied clinically important blood collection tube-related analytical/preanalytical interferences in endocrine testing. During investigation of blood collection tubes for interference on some immunoassays, primarily total triiodothyronine, by the tube surfactant found in Becton-Dickinson SST tubes, we observed an increase in the measured total free fatty acid concentrations when blood was collected in SST compared to Vacuette tubes. This prompted a detailed evaluation of blood collection tubes on serum free fatty acid concentrations. Free fatty acids are used by the liver for energy and triglyceride production and excess free fatty acids can lead to ketone body formation, particularly beta-hydroxybutyrate, by the liver. Both serum total free fatty acids and beta-hydroxybutyrate are being measured for endocrine disorders. Therefore, we also investigated the effects of collection tube types on the measurement of serum beta-hydroxybutyrate concentration. Based on our previous studies showing a significantly higher serum total triiodothyronine concentration when blood was collected in SST compared to Vacuette and glass tubes, we investigated whether the observed increase in serum free fatty acid concentration in SST compared to Vacuette tubes is due to the same type of interference as that found for serum total triiodothyronine. It appears that unidentified component(s) from the separator gel in SST, reformulated SST and PPT tubes are responsible for the falsely high free fatty acid concentration compared to other tube types examined. In contrast to total triiodothyronine, generation of falsely high free fatty acid results requires exposure of whole blood and does not occur with exposure of serum to tube constituent(s). We also propose that the approach employed in our investigations be used as a general model for assessing interference(s) from tube constituent(s).